{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:41:14Z","timestamp":1790336474170,"version":"4.1.0"},"reference-count":24,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2016,6,9]]},"published-print":{"date-parts":[[2017,1]]},"abstract":"\n Background<\/jats:title>\n \n Tumours of appendix, including classic carcinoid tumour (CCT), goblet cell carcinoid (GCC), low-grade appendiceal mucinous neoplasm, high-grade appendiceal mucinous neoplasm\/mucinous carcinoma (MCA) and non-mucinous adenocarcinoma (NMA), show different and sometimes mixed morphological features. It was hypothesised that these tumours originate from common tumour stem cell(s) with potential of various cell lineage differentiation. In normal intestinal epithelium, absorptive lineage (enterocytes) differentiation is driven by\n Notch<\/jats:italic>\n -\n Hes1<\/jats:italic>\n pathway, while secretory lineage is driven by\n Wnt-Math1<\/jats:italic>\n pathway and further separated by different downstream signallings into three sublineages (\n Gfi1<\/jats:italic>\n -\n Klf4<\/jats:italic>\n \/\n Elf3<\/jats:italic>\n for goblet cells,\n Gfi1<\/jats:italic>\n -\n Sox9<\/jats:italic>\n for Paneth cells and\n Ngn3<\/jats:italic>\n -\n Pdx1<\/jats:italic>\n \/\n Beta2<\/jats:italic>\n \/\n Pax4<\/jats:italic>\n for enteroendocrine cells).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The expressions of various signalling proteins in different appendiceal tumours were detected by immunohistochemistry on tumour tissue microarray.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n CCT showed reduced\n Hes1<\/jats:italic>\n \/\n Elf3<\/jats:italic>\n and\n Sox9<\/jats:italic>\n \/\n Klf4<\/jats:italic>\n coupled with elevated\n Math1<\/jats:italic>\n , in keeping with endocrine phenotype. As compared with CCT, GCC showed higher\n Klf4<\/jats:italic>\n and similar\n Ngn3<\/jats:italic>\n \/\n Pax4<\/jats:italic>\n , indicative of a shift of differentiation towards goblet cells as well as endocrine cells. GCC displayed a\n Notch<\/jats:italic>\n signalling similar to adenocarcinoma. Mucinous tumours showed lower\n Elf3<\/jats:italic>\n than normal appendiceal epithelium and higher\n Math1<\/jats:italic>\n \/\n Gfi1<\/jats:italic>\n \/\n Klf4<\/jats:italic>\n , suggestive of a differentiation towards less enterocytes but more goblet cells. NMA showed\n Notch<\/jats:italic>\n signalling similar to other glandular tumours, but lower\n Klf4<\/jats:italic>\n . However, some seemingly paradoxical changes were also observed, probably suggesting gene mutations and\/or our incomplete understanding of the intestinal cell differentiation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Wnt<\/jats:italic>\n \/secretory lineage protein and\n Notch<\/jats:italic>\n \/absorptive lineage protein expression profiles are generally associated with the tumour cell differentiation and morphological diversity of common appendiceal tumours.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/jclinpath-2016-203645","type":"journal-article","created":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T23:34:07Z","timestamp":1467416047000},"page":"40-50","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Differing expression profiles of\n Notch<\/i>\n \/enterocyte and\n Wnt<\/i>\n \/secretory lineage signallings are associated with morphological diversity of appendiceal tumours"],"prefix":"10.1136","volume":"70","author":[{"given":"Xianyong","family":"Gui","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziran","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yarrow J","family":"McConnell","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent G","family":"Falck","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lloyd A","family":"Mack","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walley J","family":"Temple","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, 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